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Summary

Our lab studies how individual cells translate internal and external signals into decisions such as growth, death, movement or differentiation. We quantitatively measure the changes in level, activity, or localization of proteins in single cells at high temporal resolution and correlate these behaviors with specific cellular fates. By visualizing how dynamical behaviors vary between different cells, we aim to tease out the reasons for varying behavior both in cell populations and in different cell types. Understanding these issues will be enormously important for understanding how drugs act on different cell types and organs, and to begin to gain insights into the reasons why different cells and people respond differently to specific drugs.

We mainly focus on two networks; the p53 network and the DNA damage response. In the p53 network we are investigating the dynamics of the tumor suppressor protein p53 in response to irradiation and chemotherapeutics drugs in individual cells and ask how p53’s dynamic behavior is controlled, why different cells show different dynamical behaviors and what consequences these behaviors have on cell survival. In the DNA damage response we ask how the kinetics of DNA repair and the choice of repair mechanism are affected by the cell cycle and what are the consequences of activating one repair mechanism versus the other under various cellular backgrounds.

In the long term we are optimistic that these studies will help us predict how signaling networks in human cells will behave in response to new stimuli; how they can be modified or rebuilt to give a desired cellular output; and how to selectively increase the tendency for cancer cells to go in the direction of apoptosis by modulating the dynamics of the networks controlling this decision.